This is a proposal for continuing, long-term study of kinetics of permeability of certain biological membranes and their modifications by certain peptide hormones, particularly insulin. There are two main objectives. (1) A study of mammaliam skeletal muscle has led to a two-component model in which material exchanges between sarcoplasm and interstitial fluid by either or both of two routes, one across the sarcolemma, the other across the wall of longitudinal sarcoplasmic reticulum and possibly of transverse reticulum. It is proposed to continue to test the model, which gives a new picture of intracellular ionic concentration, of differential membrane permeability, of kinetics of movement across these barriers, and for sites of action of certain agents. (2) A unitary hypothesis has been developed to account for actions of peptide hormones, particularly insulin. The hypothesis involves association between hormone and outer elements of susceptible cell membrane, re-organization of the membrane as a means of transmitting information to the interior, with modulation of permeability and of membrane-linked transport and synthesizing systems. Tests of the hypothesis will be made on isolated adipose cells and on membrane fragments from skeletal muscle. BIBLIOGRAPHIC REFERENCES: Horn, L.W. and K.L. Zierler. 1975. Effects of external potassium on potassium efflux and accumulation by rat adipocytes. J. Physiol. 253:207-222. Cheng, L., E. Rogus and K. Zierler. 1976. Catechol, a structural requirement for Na,K-ATPase stimulation in rat skeletal muscle membrane. Fed. Proc. (in press).